Resveratrol Nanoparticle System Improves Dissolution Properties and Enhances the Hepatoprotective Effect of Resveratrol through Antioxidant and Anti-Inflammatory Pathways

Abstract

Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection. Unfortunately, RES is restricted in clinical application due to poor dissolution property and adsorption. In addition, red wine as a supplement for preventing disease is not recommended for patients with alcohol-related disorders. To address these limitations, we successfully developed a novel RES nanoparticle system (RESN) and demonstrated that RESN could circumvent the physicochemical drawbacks of raw RES with respect to dissolution, such as the reduction of particle size, amorphous transformation, and hydrogen-bond formation. In addition, we employed an animal model of CCl₄-induced hepatotoxicity to estimate the potential of the nanoparticle formulation to improve the hepatoprotective effect of orally administered RES. Our results demonstrated that RESN can diminish liver function markers (aspartate aminotransferase and alanine aminotransferase) by decreasing hepatocyte death due to CCl₄-induced hepatotoxicity in rats, when compared with RES administration. The effect was achieved by reducing oxidative stress (decreased reactive oxygen species and lipid peroxidation) and lowering inflammatory cytokines (decreased tumor necrosis factor-α and interleukin 1β) and protein expression (cyclooxygenase-2, inducible nitric oxide synthase, cytosolic phospholipase A2, and caspase-3). In conclusion, enhancement of the dissolution of RES through a nanoparticle engineering process can result in increased hepatoprotective effects mediated by antioxidant and anti-inflammatory activities. Consequently, we suggest that RESN deserves further study, perhaps in prophylaxis of chronic liver diseases.

Development of novel cationic chitosan- and anionic alginate–coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol

“…The DSC curve of RSV showed the characteristic endothermic peaks corresponding to the melting point at 270°C and to the glass transition point at 363°C. 64 The disappearance of the RSV melting peak in the DSC thermograms of RSV-loaded NPs ( Figure 6C) indicates the absence of the drug crystalline state, suggesting that entrapped RSV is in an amorphous state of a solid molecular dispersion into the polymer matrix. 65 Furthermore, in the thermogram of RSV-loaded PLGA NPs, the endothermic peak of PLGA appeared at about 375°C, as observed in the pure PLGA.…”

Controlled formation and stabilization of nanosized colloidal suspensions by combination of soy protein and biosurfactant stevioside as stabilizers

“…The entrapment efficiency and yield of RESN were determined according to the method described previously with some modifications (Lee et al, 2012;Venkateswarlu & Manjunath, 2004). For the RESN yield, 1 mL of RESN was added to 9 mL of acetonitrile and stirred for 5 min, and the contained RES concentration was measured by HPLC.…”

“…Quantitative analysis of RES was performed according to the method described in the previous study . The yield and entrapment efficiency of RESN can be calculated by the following equations (Lee et al, 2012;Venkateswarlu & Manjunath, 2004 Transmission electron microscopy (TEM) was used to observe the surface morphology of RESN and to further confirm particle diameter by DLS. Samples were prepared by the negative-staining method.…”

“…The determination of entrapment efficiency and yield is the best method to evaluate the amount of active compounds successfully encapsulated in nanosuspension formulations (Lee et al, 2012). The entrapment efficiency largely depends on the size of nanosuspensions and thus the stabilizer compositions (Sinha et al, 2013;Thorat & Dalvi, 2012).…”

Preparation and Drug Release Study of Novel Nanopharmaceuticals with Polysorbate 80 Surface Adsorption

“…In preparing conventional formulations for craniocerebral diseases, increasing the drug solubility often requires a number of drug additions, which results in toxicity. Currently, about 40% of clinically used drugs have limited use because of poor dissolution [7,8].…”